FDA Finalizes Postmarket Device Surveillance Guidance

By McKenzie E. Cato* & Allyson B. Mullen –

On May 16, FDA issued its final guidance document on postmarket surveillance of medical devices, “Postmarket Surveillance Under Section 522 of the Federal Food, Drug, and Cosmetic Act,” approximately five years after issuing the draft guidance. The stated purpose of this guidance is to assist manufacturers in fulfilling section 522 obligations by providing recommendations on the format, content, and review of postmarket surveillance plan submissions.  The final guidance outlines the section 522 postmarket surveillance process from initial identification of an issue through creation of a surveillance plan and submission of interim and final reports.

FDA’s postmarket surveillance program has been, and continues to be, a work in progress. About a year after issuing the draft guidance, FDA published a white paper titled “Strengthening Our National System for Medical Device Postmarket Surveillance” (see our previous post on FDA’s action plan here). One outcome from this action plan was the creation of a multi-stakeholder Planning Board via the Brookings Institution in 2014.  The Board issued a 75-page report documenting its recommendations and a 5-year implementation plan for a National Medical Device Postmarket Surveillance System in February 2015 (see our post on this report here).

The Brookings report pointed out that a “key challenge” in conducting section 522 studies is a lack of incentives for clinicians and patients to participate due to the “reporting burdens and other requirements on top of their usual practice.” The report identified registry-based surveillance as a possible solution to this problem.  The final guidance incorporated this suggestion and added “Comprehensive, Linked, Registry-Based Surveillance” to its list of postmarket surveillance study designs.  The final guidance explains that this design “leverages national registry infrastructure” and “is characterized by shared responsibilities of multiple stakeholders.”

The most notable changes from the draft guidance are the addition of procedures for increased status monitoring, review, and communication between manufacturers and the Agency. First, FDA has created a system of “decision letters” for evaluating a proposed surveillance plan.  After evaluating whether a proposed plan “is administratively complete and whether the plan will result in the collection of useful data,” FDA may issue one of the following letters:

• Not Acceptable Letter: The submission is found to be administratively incomplete.
• Approval Letter: FDA approves of the proposed plan as submitted.
• Minor Deficiency Letter: There are minor deficiencies that must be addressed before the plan is approved.
• Major Deficiency Letter: There are serious deficiencies relating to whether the plan will result in the collection of useful data that will answer surveillance questions.
• Disapproval Letter: FDA disapproves of the plan as submitted because FDA has determined that it is not likely to result in the collection of useful data that will address the postmarket surveillance questions in the 522 order.

Requests from a manufacturer to revise an approved surveillance plan would be subject to the same decision letter process. In contrast, the draft guidance merely stated that FDA would issue an approval order, an approvable letter requesting revisions, or a letter disapproving the proposed plan.  The final guidance includes a new “Section 522 Administrative Checklist” in an appendix.  In the last few years, FDA has implemented several new administrative reviews for submissions, such as the 510(k) “Refuse to Accept Policy” checklist and the pre-submission guidance (finalized in 2014), which includes a “Q-Sub Acceptance Checklist.”  This new Section 522 Administrative Checklist will hopefully be helpful to companies in avoiding “Not Acceptable” letters.

Additionally, the draft guidance included a list of categories that FDA may use in determining postmarket surveillance plan status: Plan Pending, Plan Overdue, Study Pending, Progress Adequate, Progress Inadequate, Completed, Terminated, and Other.  The final guidance added several new categories to this list:  Noncompliant, Revised/Replaced, and Consolidated.  According to a September 2015 GAO report, of the postmarket surveillance studies ordered by FDA from May 1, 2008, through February 24, 2015, 88% are inactive. About one-third of the studies classified as “inactive” were studies that were consolidated with other related study orders.  The additional status categories in the final guidance, particularly the addition of a “Consolidated” category, appears to be an attempt to better track the outcome of the vast majority of postmarket surveillance studies which become inactive.

The final guidance does not incorporate any significant changes to the recommended content and format of interim and final reports. However, one comment by AdvaMed on the draft guidance criticized the vagueness of the language used by FDA in describing the criteria the Agency uses to evaluate interim and final reports (e.g., “the completeness of the report”).   FDA has added some additional language to clarify these criteria.  For example, in regards to the “completeness” of an interim report, the final guidance explains that FDA will review “progress towards achieving primary and secondary endpoints and performance goals, or sufficient individual endpoint data to infer progress in the case of composite endpoints.”  The final guidance also adds that if an interim report includes insufficient data or raises new safety or effectiveness concerns, FDA may take certain regulatory actions, including requesting labeling changes, issuing safety communications, or even taking compliance and/or enforcement action.

FDA has greatly expanded the list of postmarket surveillance information that may be posted publicly on FDA’s 522 webpage. In addition to general information about postmarket surveillance studies (e.g., application number, applicant name, device name, status) and reporting information (e.g., interim and final report schedule, receipt dates, status category), which were listed in the draft guidance, the final guidance states that the following additional information may be posted on the 522 webpage:

• General surveillance plan parameters: Design description, data source, comparison group, analysis type, patient population
• Detailed surveillance plan parameters, where applicable: Design description, sample size (patients and sites), patient population description, data collection, follow-up visits and length of follow-up
• Interim report results: Interim summary data and/or FDA analyses “when appropriate to protect the public health,” including number of patients enrolled, number of sites enrolled, and interim safety/effectiveness findings
• Final report results, where applicable: Actual number of patients enrolled, actual number of sites enrolled, patient follow-up date, final safety/effectiveness findings, study/surveillance strengths and weaknesses

General and detailed study parameters and report results are already posted on FDA’s section 522 website, so it is unclear whether the final guidance was updated to reflect existing policy or whether FDA plans to post even more specific information about postmarket surveillance plans moving forward.

Since the draft guidance was issued in August 2011, the Food and Drug Administration Safety and Innovation Act (FDASIA) amended section 522 to provide that FDA may issue a postmarket surveillance order at the time of device approval or clearance or any time thereafter. FDASIA also specified that a manufacturer must commence postmarket surveillance within 15 months after the order is issued.  The final guidance has been edited to reflect these timing considerations.  The guidance notes that failure to commence surveillance within the 15-month period is a prohibited act which renders the device misbranded. 

Finally, the final guidance expands on the section about repercussions for failure to comply with a section 522 order. Unless an exemption is granted, manufacturers must comply with the order, even if the manufacturer has stopped marketing the device subject to the order.  The guidance states that FDA will review requests to terminate or modify a postmarket surveillance plan on a case-by-case basis, but notes that FDA is less likely to grant such requests for devices that are implanted long-term.  

Companies should note that 522 orders are appealable. The final guidance reiterates section 822.22 of the regulations, indicating that if a manufacturer disagrees with FDA about the content of a surveillance plan or a proposed plan is disapproved, the manufacturer has several procedural options.  A manufacturer may request a meeting with the Office Director of OSB, appeal FDA’s decision in accordance with 21 C.F.R. § 10.75, request an informal hearing under 21 C.F.R. Part 16, or request review by the Medical Devices Dispute Resolution Panel of the Medical Devices Advisory Committee.  While not used frequently (according to FDA’s website only 4 were issued last year), manufacturers are often required to expend a great deal of time and resources to comply.  We hope that the final guidance provides those manufacturers faced with a 522 order greater clarity as to the process and details for compliance. 

*Summer Associate